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Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy

Khan, KN; Kasilian, M; Mahroo, OAR; Tanna, P; Kalitzeos, A; Robson, AG; Tsunoda, K; ... Michaelides, M; + view all (2018) Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy. Ophthalmology , 125 (5) pp. 735-746. 10.1016/j.ophtha.2017.11.020. Green open access

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PURPOSE: To describe the earliest features of ABCA4-associated retinopathy. DESIGN: Case series. PARTICIPANTS: Children with a clinical and molecular diagnosis of ABCA4-associated retinopathy without evidence of macular atrophy. METHODS: The retinal phenotype was characterized by color fundus photography, OCT, fundus autofluorescence (FAF) imaging, electroretinography, and in 2 patients, adaptive optics scanning laser ophthalmoscopy (AOSLO). Sequencing of the ABCA4 gene was performed in all patients. MAIN OUTCOME MEASURES: Visual acuity, OCT, FAF, electroretinography, and AOSLO results. RESULTS: Eight children with ABCA4-associated retinopathy without macular atrophy were identified. Biallelic variants in ABCA4 were identified in all patients. Four children were asymptomatic, and 4 reported loss of VA. Patients were young (median age, 8.5 years; interquartile range, 6.8 years) with good visual acuity (median, 0.155 logarithm of the minimum angle of resolution [logMAR]; interquartile range, 0.29 logMAR). At presentation, the macula appeared normal (n = 3), had a subtly altered foveal reflex (n = 4), or demonstrated manifest fine yellow dots (n = 1). Fundus autofluorescence identified hyperautofluorescent dots in the central macula in 3 patients, 2 of whom showed a normal fundus appearance. Only 1 child had widespread hyperautofluorescent retinal flecks at presentation. OCT imaging identified hyperreflectivity at the base of the outer nuclear layer in all 8 patients. Where loss of outer nuclear volume was evident, this appeared to occur preferentially at a perifoveal locus. Longitudinal split-detector AOSLO imaging in 2 individuals confirmed that the greatest change in cone spacing occurred in the perifoveal, and not foveolar, photoreceptors. Electroretinography showed a reduced B-wave-to-A-wave ratio in 3 of 5 patients tested; in 2 children, recordings clearly showed electronegative results. CONCLUSIONS: In childhood-onset ABCA4-associated retinopathy, the earliest stages of macular atrophy involve the parafovea and spare the foveola. In some cases, these changes are predated by tiny, foveal, yellow, hyperautofluorescent dots. Hyperreflectivity at the base of the outer nuclear layer, previously described as thickening of the external limiting membrane, is likely to represent a structural change at the level of the foveal cone nuclei. Electroretinography suggests that the initial site of retinal dysfunction may occur after phototransduction.

Type: Article
Title: Early Patterns of Macular Degeneration in ABCA4-Associated Retinopathy
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.ophtha.2017.11.020
Publisher version: https://doi.org/10.1016/j.ophtha.2017.11.020
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10041586
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